Mutations or deletions in the survival of motor neuron 1 (SMN1) gene that decreases the SMN protein expression result in spinal muscular atrophy (SMA), a genetically inherited disease that causes progressive muscle degeneration and infant deaths. Functionally, SMN forms a complex with other proteins including Gemins 2-8 and Unrip. The SMN complex is essential for the biogenesis of spliceosomal nuclear ribonucleoproteins and it is involved in translocation of beta-actin to axonal growth cones. Currently, it is unclear how loss of SMN function leads to selective motor-neuron cell death. Animal models have demonstrated that increase of the SMN protein level can rescue the disease phenotype, suggesting that stabilization of the SMN protein is an extremely promising strategy for SMA treatment. In this study, we will employ biochemical, cell biological and next- generation genomic sequencing techniques to determine mechanisms by which the SMN complex assembly, stability and functions are regulated by SMN ubiquitination/deubiquitination. Our study might discover a deubiquitinating enzyme as a novel regulator of the SMN complex and thus, identify a novel therapeutic target for SMA.